A chemical synthesis method of solanine and its derivatives

Abstract

The present invention discloses a chemical synthesis method of solanine and its derivatives, belonging to the field of carbohydrate chemistry. A method for preparing a compound shown in Formula I, the method comprising glycosidating compound 4 with compound 3 or 5 under the coordinated catalysis of gold (III) ions and nitrile compounds to obtain compound 16 or 15; and a deprotection step; wherein X is NH or O; wherein the structures of compounds 3, 4, 5, 15 and 16 are as follows: The present invention establishes a glycosidation method under the coordinated catalysis of gold (III) ions and nitrile compounds, efficiently glycosidating compound 4 with compound 3 or compound 5, and obtaining compound 16 or compound 15 in a β-configuration in a high yield.

Description

Technical Field

[0001] The present invention belongs to the field of carbohydrate chemistry, and in particular relates to an efficient and simple convergent chemical synthesis method for synthesizing solanine and its derivatives. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance understanding of the overall background of the invention and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to those skilled in the art.

[0003] Glycoalkaloids are secondary metabolites found in plants of the Solanaceae family, such as potatoes, potatoes, and eggplant. They primarily protect the plant from pathogens and predators. They possess a variety of pharmacological effects, including antibiotic, antifungal, antibacterial, and antiviral properties. Solanine is a typical spirostane-type glycoalkaloid isolated from Solanum species. It consists of a hydrophilic sugar chain (solanose triose) and a hydrophobic aglycone (solanamine). Solanose triose includes β-D-galactose, β-D-glucose, and α-L-rhamnose. Solanamine has a steroidal skeleton with 27 carbon atoms, with the only heteroatom being a nitrogen atom at position C-26. Research has shown that solanine has important ecological benefits for plants, such as inhibiting the growth of the pest red flour beetle and exhibiting allelopathic effects, inhibiting the growth of larvae of plants other than Solanum species. Solanine also exhibits potent physiological activities, such as inhibiting tumor cell proliferation and having antifungal and anticancer properties. Recently, researchers discovered that solanine can induce ferroptosis and kill tumor cells. Although solanine has potential biological significance, current research on its activity and mechanism of action still relies on extraction and isolation from natural products. The content of glycoalkaloids in plants is relatively low, with solanine containing only 1%. The structural similarity of glycoalkaloids also poses certain difficulties in isolation and purification. Therefore, how to efficiently and efficiently prepare glycoalkaloids of a single configuration has become a key task for researchers. Due to substrate specificity and the lack of enzymes, enzymatic synthesis is not an effective approach. However, chemical synthesis, with its flexibility and versatility, has become a powerful means. In recent decades, researchers have made great efforts in the synthesis of steroidal glycoalkaloids, but the effective construction of compounds containing glycosylation structures at the 2nd position remains a major synthetic obstacle. Linear synthesis of the 2nd-position β-glycosidic bond usually requires the use of a temporary 2nd-position acyl protecting group, which requires selective protection and deprotection operations.

[0004] Although researchers have explored various strategies, including remote participation, intramolecular glycosyl delivery (IAD), and helium-directed glycosyl delivery (HAD), in order to improve the stereoselectivity of the synthesis, these methods all introduce complex protection and deprotection group operations, which seriously restrict the overall efficiency of the synthesis process. Therefore, to date, there is no technology that can achieve efficient and large-scale preparation of solanine and its derivatives. This situation highlights the limitations of the current synthesis method and makes the efficient preparation of solanine and its derivatives a synthetic problem. Summary of the Invention

[0005] In order to solve the deficiencies of the prior art, the present invention aims to provide a chemical synthesis method of solanine and its derivatives. The chemical synthesis method provided by the present invention is characterized by high efficiency and simplicity.

[0006] In order to achieve the above object, the technical solution of the present invention is:

[0007] The first aspect of the present invention provides a method for preparing a compound represented by formula I.

[0008]

[0009] wherein X is -NH- or -O-;

[0010] The method comprises the steps of glycosidating compound 4 with compound 3 or 5 under the coordinated catalysis of gold (III) ions and nitrile compounds to obtain compound 16 or 15; and a deprotection step;

[0011] Among them, the structures of compounds 3, 4, 5, 15 and 16 are shown below:

[0012]

[0013] When X is -NH-, the compound represented by formula I is solanine; when X is O, the compound represented by formula I is a natural derivative of solanine.

[0014] The natural derivatives of solanine prepared in this invention are also extracted from Solanum genus plants and are divided into two parts: solanose and diosgenin. Research on its derivatives helps to deepen the understanding of the mechanism of action and biological activity of solanine and its derivatives.

[0015] The invention provides a gold (III)-nitrile coordinated catalytic glycosidation glycosylation method for realizing efficient selective connection of a glycosyl donor and aglycone, and can catalyze donors without adjacent group participation or remote group participation.

[0016] In some embodiments of the present invention, when compound 4 is subjected to glycosidation reaction with compound 3, the method further comprises: before deprotection, reducing the azide group in compound 16 to an amino group.

[0017] In some embodiments of the present invention, the nitrile compound is trimethylacetonitrile.

[0018] In some embodiments of the present invention, the preparation method of compound 4 comprises the following steps:

[0019] Compound 6 and compound 7 were glycosylated to obtain compound 13;

[0020] Converting compound 13 into compound S1;

[0021] Converting compound S1 into compound 4;

[0022] Among them, the structures of compounds 6, 7, 13 and S1 are shown below:

[0023]

[0024] In some embodiments of the present invention, the conversion of compound 13 into compound S1 comprises the following steps:

[0025] Compound 13 was dissolved in a mixed solution of acetonitrile and water, and ammonium cerium nitrate was added at low temperature to react. After the reaction was completed, compound S1 was obtained.

[0026] Preferably, the low temperature is -2 to 2°C.

[0027] In some embodiments of the present invention, the conversion of compound S1 into compound 4 comprises the following steps:

[0028] Compound S1 was dissolved in an organic solvent, and trichloroacetonitrile and 1,8-diazabicyclo[5.4.0]undec-7-ene were added in sequence under an ice-water bath. The temperature was naturally raised to react. After the reaction was completed, compound 4 was obtained.

[0029] Preferably, the organic solvent comprises dichloromethane.

[0030] In some embodiments of the present invention, the preparation method of compound 7 comprises the following steps:

[0031] Converting compound 10 into compound 9;

[0032] Compound 9 and compound 8 were subjected to glycosylation reaction to obtain compound 11;

[0033] Converting compound 11 into compound 12;

[0034] An acylating agent was used to selectively protect the 4- and 6-hydroxyl groups in compound 12 to obtain compound 7;

[0035] Among them, the structures of compounds 8, 9, 10, 11 and 12 are shown below:

[0036]

[0037] In some embodiments of the present invention, the conversion of compound 10 into compound 9 comprises the following steps:

[0038] Compound 10 was dissolved in an organic solvent, 2,6-lutidine was added under a protective atmosphere, and the mixture was stirred at low temperature. Then, tert-butyldimethylsilyl trifluoromethanesulfonate was added and the mixture was stirred to react. After the reaction was completed, compound 9 was obtained.

[0039] Preferably, the organic solvent comprises N,N-dimethylformamide.

[0040] Preferably, the low temperature is -55 to -45°C.

[0041] In some embodiments of the present invention, the conversion of compound 11 into compound 12 of formula comprises the following steps:

[0042] Tetrabutylammonium fluoride solution was added to compound 11, and the mixture was stirred at room temperature to react. After the reaction was completed, compound 12 was obtained.

[0043] Preferably, in the tetrabutylammonium fluoride solution, the solvent is tetrahydrofuran.

[0044] In some embodiments of the present invention, the acylating agent is benzoyl chloride;

[0045] Utilizing the cyanide effect of benzoyl cyanide, compound 12 was reacted in a one-pot reaction at low temperature to obtain compound 7 with selective protection at the 4 and 6 positions.

[0046] Preferably, the low temperature is -80 to -75°C.

[0047] The invention uses a regioselective benzoylation system with benzoyl cyanide as an acylating agent to perform selective protection, thereby avoiding tedious protection and deprotection operations.

[0048] The beneficial effects of the present invention are:

[0049] This invention provides an efficient and simple convergent synthesis route for the glycoalkaloid solanine and its derivatives. Firstly, the invention utilizes the cyanide effect of benzoyl cyanide to convert compound 12 to the 4- and 6-selectively protected disaccharide acceptor compound 7 in a single pot at -78°C with an 80% yield, eliminating time-consuming protection and deprotection procedures. Secondly, the invention also establishes a novel synergistic glycosylation method using gold trichloride as a catalyst and trimethylacetonitrile as a ligand, efficiently glycosidating the glycosyl donor 4 with the aglycone acceptor 3 or 5, yielding the β-configured compound 16 or compound 15 in high yield.

[0050] The method for synthesizing the alkali solanine and its derivatives is simple to operate, has readily available raw materials, is highly practical, has a high yield, and is low in cost, and is of great significance for the industrial production of such substances. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] The accompanying drawings, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0052] Figure 1 The NMR of compound 9 prepared in Example 1 of the present invention is 1 H spectrum;

[0053] Figure 2 The NMR of compound 11 prepared in Example 1 of the present invention 1 H spectrum;

[0054] Figure 3 The NMR of compound 11 prepared in Example 1 of the present invention is 13 C spectrum;

[0055] Figure 4 The NMR of compound 12 prepared in Example 1 of the present invention 1 H spectrum;

[0056] Figure 5 The NMR of compound 12 prepared in Example 1 of the present invention 13 C spectrum;

[0057] Figure 6 The NMR of compound 7 prepared in Example 1 of the present invention is 1 H spectrum;

[0058] Figure 7 The NMR of compound 7 prepared in Example 1 of the present invention is 13 C spectrum;

[0059] Figure 8 The NMR of compound 13 prepared in Example 2 of the present invention 1 H spectrum;

[0060] Figure 9 The NMR of compound 13 prepared in Example 2 of the present invention 13 C spectrum;

[0061] Figure 10 The NMR of compound 4 prepared in Example 2 of the present invention is 1 H spectrum;

[0062] Figure 11 The NMR of compound 4 prepared in Example 2 of the present invention is 13 C spectrum;

[0063] Figure 12 The NMR of compound 16 prepared in Example 3 of the present invention is 1 H spectrum;

[0064] Figure 13 The NMR of compound 16 prepared in Example 3 of the present invention is 13 C spectrum;

[0065] Figure 14 The NMR of compound 17 prepared in Example 3 of the present invention is 1 H spectrum;

[0066] Figure 15 The NMR of compound 17 prepared in Example 3 of the present invention is 13 C spectrum;

[0067] Figure 16 The NMR of compound 1 prepared in Example 3 of the present invention is 1 H spectrum;

[0068] Figure 17 The NMR of compound 1 prepared in Example 3 of the present invention is 13 C spectrum;

[0069] Figure 18 The NMR of compound 15 prepared in Example 4 of the present invention 1 H spectrum;

[0070] Figure 19 The NMR of compound 15 prepared in Example 4 of the present invention 13 C spectrum;

[0071] Figure 20 The NMR of compound 2 prepared in Example 4 of the present invention is 1 H spectrum;

[0072] Figure 21 The NMR of compound 2 prepared in Example 4 of the present invention is 13 C spectrum. DETAILED DESCRIPTION

[0073] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0074] The raw materials and reagents used in the following examples are all conventional commercially available products and can be purchased.

[0075] Example 1

[0076] 1.1 Chemical synthesis of 4-methoxyphenyl 2-O-(2,3,4-tri-O-acetyl-α-L-rhamnopyranosyl)-4,6-di-O-benzoyl-β-D-galactopyranoside (Compound 7)

[0077] 1.2 Synthesis route of disaccharide glycosyl acceptor (Compound 7)

[0078]

[0079] 1.3 Specific experimental steps:

[0080] Preparation of compound 9

[0081] Compound 10 (2 g, 5.3 mmol) was dissolved in 18 mL of N,N-dimethylformamide, and 2,6-lutidine (1.9 mL, 15.9 mmol) was added under argon protection. The mixture was stirred at -50°C for 20 min, and TBSOTf (tert-butyldimethylsilyl trifluoromethanesulfonate) (2.4 mL, 10.6 mmol) was added. The mixture was stirred for 0.5 h. TLC detection showed that the reaction of the raw material was complete. A saturated sodium bicarbonate solution was added to quench the reaction. After dilution with 200 mL of dichloromethane, the filtrate was washed with a saturated sodium bicarbonate solution and sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated, and separated by silica gel column chromatography (petroleum ether:ethyl acetate = 6:1) to give compound 9 (2.3 g, 88%) as a white solid.

[0082] Preparation of compound 11

[0083] Add the reaction flask Molecular sieves were added to a flask under vacuum, cooled to room temperature, and then purged with argon. Compound 8 (3.8 g, 8.8 mmol, glycosyl donor) and compound 9 (3.9 g, 8.0 mmol, glycosyl acceptor) were added sequentially and dissolved in 80 mL of freshly distilled dichloromethane. The mixture was stirred at room temperature for 5 minutes, then cooled to 0°C and TMSOTf (163 μL, 0.9 mmol) was added. The mixture was allowed to react at this temperature for 10 minutes. TLC confirmed the complete reaction. The reaction was quenched with triethylamine, diluted with dichloromethane, and the molecular sieves were filtered through a pad of celite. The filtrate was washed sequentially with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (dichloromethane:methanol = 20:1) to obtain compound 11 (5.7 g, 95%) as a white solid. 1 HNMR (400MHz, CDCl3) δ7.53 (dd, J=7.5, 2.2Hz, 2H, ArH), 7.39–7.33 (m, 3H, ArH), 7. 02–6.98(m,2H,ArH),6.84–6.80(m,2H,ArH),5.50(s,1H,PhCH),5.39(dd,J=3.4,1. 7Hz, 1H, 2a-H), 5.27 (d, J=1.6Hz, 1H, 1b-H), 5.21 (dd, J=10.1, 3.5Hz, 1H, 3a-H), 5. 05(t,J=10.1Hz,1H,4a-H),4.90(d,J=7.9Hz,1H,1a-H),4.46–4.38(m,1H,5a-H),4. 34(dd,J=12.3,1.4Hz,1H,6b-H), 4.24(dd,J=9.4,7.9Hz,1H,2b-H), 4.07(td,J=5. 3,4.7,1.8Hz,2H,6b-H,4b-H),3.96(dd,J=9.4,3.6Hz,1H,3b-H),3.78(s,3H,OCH3) ,3.50(s,1H,5b-H),2.11(s,3H,COCH3),2.00(s,3H,COCH3),1.96(s,3H,COCH3),1. 20(d,J=6.3Hz,3H,6a-CH3),0.86(s,9H,tert-Butyl),0.11(d,J=7.2Hz,6H,SiMe). 13C NMR (100MHz, CDCl3) δ175.0,174.8,174.6,160.1,156.0,142.5,133.6,132.8,130.9,123.3,119.3,105.5,105.2,103.1,10 3.0,81.1,79.9,79.0,75.7,74.4,74.1,73.9,71.3,71.2,60.4,30.4,25.8,25.84,25.62,22.8,22.0,0.7.HRMS(ESI)Calcd for C 38 H 52 NaO 14 Si + [M+Na] + :783.3019,found:783.3049.

[0084] Preparation of compound 12

[0085] Compound 11 (11 g, 14.5 mmol) was placed in a round-bottom flask, and 72.5 mL of TBAF (1 M in THF, 72.5 mmol) was added. The mixture was stirred at room temperature for 1 hour. TLC indicated that the reaction was complete. The reaction system was then diluted with ethyl acetate, washed sequentially with saturated ammonium chloride solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation. The crude product was then dissolved in 200 mL of 80% acetic acid and stirred at 90°C for 1 hour. TLC indicated that the reaction was complete. The mixture was cooled, concentrated, and separated by column chromatography (ethyl acetate:methanol = 10:1) to obtain compound 12 (7.2 g, 89%). 1H NMR (400MHz, CDCl3) δ7.01–6.95(m,2H,ArH),6.87–6.80(m,2H,ArH),5.37(dd,J=3.4,1.8Hz,1H,2a-H),5.32(d,J=1.8 Hz,1H,1a-H),5.22(dd,J=10.2,3.4Hz,1H,3a-H),5.08(t,J=10.0Hz,1H,4a-H),4.87(d,J=7.7Hz,1H,1b-H),4.27(dt,J =9.8,6.2Hz,1H,5a-H),4.04–3.80(m,4H,2b-H,3b-H,6b-H),3.78(s,3H,OCH3),3.60(t,J=5.3Hz,1H,5b-H),3.52–3.42 (m,2H,4b-H),2.66(s,1H),2.14(s,3H,COCH3),2.02(s,3H,COCH3),1.98(s,3H,COCH3),1.21(d,J=6.2Hz,3H,6a-CH3). 13 C NMR (100MHz, CDCl3) δ170.7,170.5,170.0,155.2,151.0,117.7,114.6,100.3,98.0,76.1, 74.3,70.9,69.7,69.5,69.3,66.5,61.3,55.6,20.8,20.73,20.70,17.3.HRMS(ESI)Calcd for C 25 H 34 NaO 14 + [M+Na] + :581.1841,found:581.1893.

[0086] Preparation of compound 7

[0087] Add the reaction flask The flask was evacuated and cooled to room temperature, then purged with argon. Compound 12 (7.1 g, 12.7 mmol) was added and dissolved in 225 mL of a 3:1 mixture of dichloromethane and N,N-dimethylformamide. Benzoyl cyanide (3.7 g, 27.9 mmol) was then added and stirred at room temperature for 5 minutes. The reaction mixture was then cooled to -78°C and 4-dimethylaminopyridine (379 mg, 3.1 mmol) was added. The reaction was allowed to react at this temperature for 5 hours. TLC confirmed the reaction was complete. Ammonium chloride and methanol were added to quench the reaction, followed by filtration through a pad of celite to remove the molecular sieves. The filtrate was washed with dichloromethane, concentrated, and separated by silica gel column chromatography (petroleum ether:ethyl acetate = 1:3) to obtain compound 7 (7.8 g, 80%) as a white solid. 1 H NMR (400MHz, CDCl3) δ8.13–8.08(m,2H,ArH),8.05–8.00(m,2H,ArH),7.59–7.53(m,2H,ArH),7.43(td,J=7.7,1.4Hz,4H,ArH),7.06–7.01(m, 2H,ArH),6.75–6.69(m,2H,ArH),5.66–5.63(m,1H,4b-H),5.39(dd,J=3.5,1.8Hz,1H,2a-H),5.32(d,J=1.8Hz,1H,1a-H),5.24(dd,J=10.1,3 .4Hz,1H,3a-H),5.10(t,J=10.0Hz,1H,4a-H),4.99(d,J=6.8Hz,1H,1b-H),4.54–4.44(m,2H,6b-H),4.40(dt,J=9.9,6.2Hz,1H,5a-H),4.22– 4.11(m,3H,2b-H,3b-H,5b-H),3.74(s,3H,OCH3),2.06(s,3H,COCH3),2.03(s,3H,COCH3),1.96(s,3H,COCH3),1.29(d,J=6.2Hz,3H,6a-CH3). 13 C NMR (100MHz, CDCl3) δ170.4,170.2,170.0,166.8,166.0,155.4,151.1,130.1,129.8,128.5,128.4,118.1,114.6,1 00.5,98.3,75.9,73.6,71.5,71.0,70.9,69.6,69.4,66.6,62.7,55.6,20.84,20.82,20.75,17.4.HRMS(ESI)Calcd for C 39 H 42 NaO 16+ [M+Na] + :789.2366,found:789.2395.

[0088] Example 2:

[0089] 2.1 Chemical Synthesis of 2-O-(2,3,4-tri-O-acetyl-α-L-rhamnopyranosyl)-3-O-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-4,6-di-O-benzoyl-α-D-galactopyranosyl trichloroacetimidate (Compound 4)

[0090] 2.2 Synthesis route of compound 4

[0091]

[0092] 2.3 Specific experimental steps:

[0093] Preparation of compound 13

[0094] Add the reaction flask Molecular sieves were added to the flask under vacuum, cooled to room temperature, and then purged with argon. Compound 6 (384 mg, 519 μmol, glycosyl donor) and compound 7 (766 mg, 415 μmol, glycosyl acceptor) were added sequentially and dissolved in 2.6 mL of freshly distilled dichloromethane. The mixture was stirred at room temperature for 5 minutes, then cooled to 0°C and TMSOTf (9.4 μL, 51.9 μmol) was added. The reaction was allowed to react at this temperature for 40 minutes. TLC confirmed the complete reaction of the starting material. The reaction was quenched with triethylamine, diluted with dichloromethane, and the molecular sieves were filtered through a celite pad. The filtrate was washed sequentially with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and separated by silica gel column chromatography (petroleum ether:dichloromethane:ethyl acetate = 6:6:1) to obtain compound 13 (500 mg, 93%) as a white solid. 11H NMR (400 MHz, CDCl3) δ 8.03 (dd, J = 14.9, 8.0 Hz, 6H, ArH), 7.92 (d, J = 7.8 Hz, 2H, ArH), 7.75 (d, J = 7.8 Hz, 2H ArH), 7.67–7.18 (m, 18H ArH), 6.99–6.91 (m, 2HArH), 6.70–6.61 (m, 2H ArH), 6.01 (t, J = 9.6 Hz, 1H, 3c-H), 5.75–5.63 (m, 2H,, 4b-H, 4c-H), 5.41 (dd, J = 9.9, 7.8 Hz, 1H, 2c-H), 5.38–5.35 (m, 1H, 2a-H), 5.31 (dd, J = 10.2, 3.5 Hz, 1H, 3a-H), 5.27 (d, J = 7.9 Hz, 1H, 1c-H), 5.24 (d, J = 1.8 Hz, 1H, 1a-H), 5.11 (t, J = 10.0 Hz, 1H, 4a-H), 4.75 (d, J = 7.3 Hz, 1H, 1b-H), 4.65 (dd, J = 12.2, 4.9 Hz, 1H, 6c-H), 4.56 (dd, J = 12.2, 3.2 Hz, 1H, 6c-H), 4.45 (qd, J = 11.6, 6.2 Hz, 2H, 6b-H), 4.34–4.16 (m, 5H, 3b-H, 2b-H, 5c-H, 5b-H, 5a-H), 3.98 (dd, J = 8.0, 4.7 Hz, 1H), 3.71 (s, 3H, OCH3), 2.14 (s, 3H, COCH3), 2.09 (s, 3H, COCH3), 2.05 (s, 2H, COCH3), 1.13 (d, J = 6.2 Hz, 3H, 6a-CH3). 13 13C NMR (100 MHz, CDCl3) δ 170.3, 170.1, 170.0, 166.0, 165.9, 165.7, 165.5, 165.1, 164.7, 155.4, 151.0, 118.1, 114.4, 100.6, 99.4, 97.8, 75.5, 72.54, 72.51, 71.8, 70.9, 70.0, 69.9, 69.8, 69.0, 67.0, 62.9, 62.7, 55.6, 20.9, 17.3. HRMS (ESI) Calcd for C 73 H 68 NaO 25 + [M+Na] + : 1367.3942, found: 1367.3985.

[0095] Preparation of Compound 4<{}

[0096] Compound 13 (1.1 g, 0.8 mmol) was dissolved in 80 mL of a 4:1 mixture of acetonitrile and water. Cerium ammonium nitrate (2.2 g, 4.1 mmol) was added at 0°C and allowed to react for 15 min. TLC confirmed the completion of the reaction. The reaction was quenched by adding saturated sodium bicarbonate solution, then diluted with ethyl acetate. The precipitate was filtered through a Celite pad. The organic phase was washed sequentially with saturated sodium bicarbonate and saturated sodium chloride solutions, dried over anhydrous sodium sulfate, filtered, and concentrated. Compound S1 was obtained by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) as a white solid. The crudely purified compound S1 (1.6 g, 1.3 mmol) from the previous step was dissolved in freshly dichloromethane. In an ice-water bath, trichloroacetonitrile (391 μL, 3.9 mmol) and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) (39 μL, 260 μmol) were added sequentially. The temperature was naturally raised and the reaction was carried out for 5 h. After TLC detection, the reaction of the raw materials was complete. The solvent was removed by rotary evaporation and the mixture was separated by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain compound 4 (1.4 g, 78%) as a white foamy solid. 1 H NMR(400MHz,CDCl3)δ8.69(s,1H,NHCCl3),8.05–7.93(m,6H,ArH),7.94–7.88(m,2H,ArH),7.76–7.71(m,2H ArH),7.56–7.29(m,11H ArH),7.21(td,J=7.8,2.0Hz,4HArH),6.51(d,J=3.7Hz,1H,1b-H),6.03–5.95(m,2H,4b-H,3c-H),5.70(t,J=9.7Hz,1H,4c-H ),5.47–5.43(t,1H,2c-H),5.39–5.34(m,2H,1c-H,2a-H),5.23(dd,J=10.2,3.1Hz,1H,3a-H),5.07(t,J=10.0Hz,1H,4a-H), 4.88(d,J=1.8Hz,1H,1a-H),4.63–4.52(m,4H,5c-H,3b-H,6c-H),4.47–4.33(m,3H,5b-H,6b-H),4.26(dd,J=9.9,3.7Hz,1H, 2b-H),3.96–3.87(m,1H,5a-H),2.12(s,3H,COCH3),2.06(s,3H,COCH3),2.02(s,3H,COCH3),1.15(d,J=6.3Hz,3H,6a-CH3). 13CNMR (100MHz, CDCl3) δ170.1,169.8,169.5,166.2,166.0,165.9,165.4,165.3,165.1,164.6,160.8,133. 3,133.2,133.13,133.07,133.03,132.96,132.9,129.93,129.86,129.8,129.73,129.66,129.64,129.58, 129.5,129.1,129.04,129.03,128.3,128.15,128.10,99.8,95.0,90.8,72.7,72.4,72.3,71.7,70.5,70. 1,69.9,69.6,69.4,69.1,67.7,63.0,62.7,60.3,21.0,20.93,20.85,20.82,20.77,17.4.HRMS(ESI)Calcd for C 68 H 62 Cl3NNaO 24 + [M+Na] + :1404.2620,found:1404.2660.

[0097] Example 3:

[0098] 3.1 Chemical synthesis of solanine (compound 1)

[0099] 3.2 Synthesis route of solanine (compound 1)

[0100]

[0101] 3.3 Specific experimental steps:

[0102] Preparation of compound 16

[0103] Add the reaction flask The mixture was dried over a vacuum oven with 5% 4% daptomycin (0.5% daptomycin), cooled to room temperature, and then purged with argon. Compound 4 (50 mg, 36.2 μmol, glycosyl donor) and compound 3 (19 mg, 43.4 μmol, glycosyl acceptor) were added sequentially and dissolved in 724 μL of a 5:1 mixture of dichloromethane and trimethylacetonitrile. The mixture was stirred at room temperature for 5 minutes. The reaction solution was then cooled to -50°C and gold trichloride (1.1 mg, 3.62 μmol) was added. The mixture was allowed to react at this temperature for 10 minutes. TLC confirmed the completion of the reaction. The reaction was quenched with triethylamine, and the molecular sieves were filtered off through a celite pad. The mixture was separated by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain compound 16 (48 mg, 81%) as a white solid. 1H NMR(400MHz,CDCl3)δ8.06–7.95(m,7H,ArH),7.93–7.86(m,2H,ArH),7.77–7.70(m,2H,ArH),7.64–7.58(m,2H,ArH),7.58–7.18(m,19H,ArH),5.96(t,J=9.6Hz,1H,3c-H),5.70–5.60(m,2H,4c-H,4b-H),5.40–5.25(m,4H,3a-H,2a-H,2c-H,5b-H),5.21–5.14(m,2H,1a-H,1c-H),5.08(t,J=9.9Hz,1H,4a-H),4.75(ddd,J=10.1,7.8,5.7Hz,1H,6c-H),4.60(dd,J=12.2,4.7Hz,1H,6c-H),4.54–4.47(m,1H,6b-H),4.47–4.31(m,3H,5a-H,6b-H,1b-H),4.19(ddd,J=21.5,8.8,3.7Hz,2H,5c-H,3b-H),3.98(dd,J=9.4,7.8Hz,1H,2b-H),3.87(dd,J=7.9,5.3Hz,1H,5b-H),3.52(tt,J=11.1,4.6Hz,1H),3.23(dd,J=12.0,5.6Hz,1H),3.10(dd,J=12.0,7.0Hz,1H),2.48(d,J=10.1Hz,1H),2.45–2.37(m,1H),2.25(dd,J=28.1,13.9Hz,1H),2.13(s,3H,COCH3),2.04(s,3H,COCH3),2.05(s,3H,COCH3),1.92–1.68(m,2H),1.60(d,J=7.0Hz,5H),1.51–1.38(m,2H),1.36–1.21(m,5H),1.15(d,J=6.2Hz,3H,6a-CH3),0.97(d,J=6.7Hz,6H),0.89(q,J=7.1,5.5Hz,3H),0.68(s,3H). 13C NMR (100MHz, CDCl3) δ170.3,170.2,170.0,166.0,165.98,165.96,165.5,165.1,164.7,151.2,140.3,133.3,133.1,133.03,133.00,132.9 1,132.88,130.1,130.0,129.9,129.88,129.80,129.77,129.71,129 .68,129.6,129.1,129.0,128.9,128.4,128.34,128.29,128.2,128.1 ,121.8,104.0,100.0,99.3,97.2,84.3,79.7,74.0,72.5,71.4,71.1 ,70.1,69.9,69.7,69.0,66.5,64.2,62.7,57.6,55.00,50.01,43.3,3 9.5,38.4,37.0,36.8,34.1,33.0,32.2,31.5,31.2,29.71,29.65,23.2,20.95,20.90,20.86,19.3,17.6,17.3,14.0,11.7.HRMS(ESI)Calcd for C 93 H 102 N3O 25 + [M+H] + :1661.6831,found:1661.6881.

[0104] Preparation of compound 17

[0105] Compound 16 (110 mg, 66.3 μmol) was dissolved in 3 mL of dry acetonitrile, and sodium iodide (20 mg, 133 μmol) was added. The mixture was stirred at room temperature for 30 min, followed by the dropwise addition of TMSCl (18 μL TMSCl dissolved in 150 μL acetonitrile, 142.5 μmol). The reaction was allowed to proceed at this temperature for 30 min, and TLC confirmed the complete reaction. The mixture was quenched by the addition of 10% sodium thiosulfate solution, and the pH of the reaction mixture was adjusted to 10 with 5% sodium hydroxide solution. After stirring for 1 h, the mixture was washed with dichloromethane and saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. The mixture was separated by silica gel column chromatography (petroleum ether:ethyl acetate:triethylamine = 1:2:0.03) to afford compound 17 (90.4 mg, 84%) as a white foamy solid. 1H NMR(400MHz,CDCl3)δ8.08–7.94(m,6H,ArH),7.90(d,J=7.8Hz,2H,ArH),7.73(d,J=7.8Hz,2H,ArH),7.61(d,J=7.7Hz,2H,ArH),7.58–7.25(m,17H,ArH),7.21(t,J=7.7Hz,2H,ArH),5.96(t,J=9.6Hz,1H,3c-H),5.68–5.61(m,2H,4c-H,4b-H),5.38–5.27(m,4H,3a-H,2a-H,2c-H,5b-H),5.21–5.15(m,2H,1a-H,1c-H),5.08(t,J=9.8Hz,1H,4a-H),4.61(dd,J=12.2,4.8Hz,1H,6c-H),4.55–4.25(m,5H,6c-H,6b-H,5a-H,6b-H,1b-H),4.25–4.14(m,2H,5c-H,3b-H),3.98(t,J=8.6Hz,1H,2b-H),3.86(dd,J=7.7,5.3Hz,1H,5b-H),3.51(tt,J=10.8,4.6Hz,1H),2.71–2.56(m,2H),2.44–2.37(m,1H),2.27(t,J=12.2Hz,1H),2.13(s,3H,COCH3),2.06(s,3H,COCH3),2.04(s,3H,COCH3),2.02–1.94(m,2H),1.89(q,J=7.2Hz,2H),1.82–1.39(m,11H),1.32–1.22(m,3H),1.15(d,J=6.2Hz,3H,6a-CH3),0.96(d,J=6.7Hz,5H),0.85(d,J=6.2Hz,3H),0.81(s,3H). 13C NMR (100MHz, CDCl3) δ170.2,170.1,169.9,166.0,165.9,165.5,165.1,164.6,140.3,133.3,133.0,132.8,130.1,1 29.9,129.8,129.7,129.6,129.2,129.0,128.9,128.38,128.36,128.3,128.13,128.07,121.8,100.1,99.4,98.3, 97.2,79.7,74.1,72.6,71.4,71.2,70.2,69.9,69.8,69.0,66.5,62.8,62.7,60.4,56.5,50.1,47.7,41.3,40.5,39 .9,38.4,37.0,36.8,34.1,32.2,31.4,30.3,29.7,20.9,20.8,19.3,19.2,17.3,16.4,15.3,14.2.HRMS(ESI)Calcd for C 93 H 104 NO 25 + [M+H] + :1635.6926,found:1635.6963.

[0106] Preparation of compound 1

[0107] Compound 17 was dissolved in a mixed solution of dichloromethane:methanol = 1:4, and 1 M sodium hydroxide was added to adjust the pH to 12. The mixture was refluxed and stirred at 70°C for 4 h. TLC detected that the reaction of the raw material was complete. The solvent was removed by rotary evaporation and separated by silica gel column chromatography (dichloromethane:methanol containing 8% water:triethylamine = 3:1:0.01) to obtain compound 1 (64 mg, 91%) as a white solid. 1H NMR (400MHz, Pyridine-d5) δ6.25(d,J=1.4Hz,1H),5.28(d,J=5.0Hz,1H),5.15(d,J=7.7Hz,1H),4.89(d,J=7.8Hz,2H),4.86(dd,J=3.2,1.7 Hz,1H),4.77(d,J=3.1Hz,1H),4.66(dd,J=9.6,7.8Hz,1H),4.56(dd,J=9.3,3.4Hz,1H),4.45–4.37(m,2H),4.34(dd,J=11.2,6.5Hz,1H),4.3 0–4.23(m,3H),4.20(dd,J=11.3,5.1Hz,1H),4.17–4.10(m,2H),3.97(t,J=6.1Hz,1H),3.90(q,J=7.3,5.8Hz,3H),2.80–2.66(m,4H),2.12– 1.97(m,2H),1.92(q,J=9.2,8.1Hz,1H),1.88–1.78(m,1H),1.78–1.13 (m,17H),1.11–0.97(m,8H),0.96–0.80(m,6H),0.77(d,J=4.5Hz,3H). 13 C NMR(150MHz,Pyridine-d5)δ140.8,121.6,105.8,102.2,100.3,98.3,84.7, 79.2,78.4,78.3,77.4,76.4,75.0,74.9,74.1,72.8,72.5,71.5,70.4,69.4 ,63.3,62.52,62.47,56.5,50.2,47.7,41.6,40.6,39.9,38.7,37.4,37.1,34.4,32.5,32.2,31.6,31.2,30.7,30.0,21.0,19.5,19.3,18.5,16.4,15.6.

[0108] Example 4:

[0109] 4.1 Chemical synthesis of solanine derivatives (compound 2)

[0110] 4.2 Synthesis route of compound 2

[0111]

[0112] 4.3 Specific experimental steps:

[0113] Preparation of compound 15

[0114] Add the reaction flask The mixture was dried over a vacuum oven with 5% 4% zeolite and cooled to room temperature, then purged with argon. Compound 4 (50 mg, 36.2 μmol, glycosyl donor) and compound 5 (19 mg, 43.4 μmol, glycosyl acceptor) were added sequentially and dissolved in 3.6 mL of a 5:1 mixture of dichloromethane and trimethylacetonitrile. The mixture was stirred at room temperature for 5 minutes. The reaction solution was then placed at -50°C and gold trichloride (1.1 mg, 3.62 μmol) was added. The mixture was allowed to react at this temperature for 10 minutes. TLC confirmed the completion of the reaction. The reaction was quenched with triethylamine, and the zeolite was filtered off through a celite pad. The mixture was separated by silica gel column chromatography (petroleum ether:ethyl acetate = 3:1) to obtain compound 15 (49.6 mg, 84%) as a semi-solid. 1 H NMR (400MHz, CDCl3) δ8.04–7.95(m,6H,ArH),7.90(d,J=7.9Hz,2H,ArH),7.73(d,J=7.7Hz,2H,ArH),7. 61(d,J=7.7Hz,2H,ArH),7.56–7.18(m,15H,ArH),5.96(t,J=9.6Hz,1H,3c-H),5.70–5.62(m,2H,4c-H,4 b-H),5.40–5.27(m,5H,2c-H,2a-H,3a-H),5.22–5.15(m,2H,1c-H,1a-H),5.08(t,J=9.7Hz,1H,4a-H), 4.61(dd,J=12.2,4.8Hz,1H,6c-H),4.54–4.30(m,6H,6c'-H,5a-H,1b-H,5b-H,6b-H,6b'-H),4.25–4.09 (m,2H,5c-H),3.98(t,J=8.6Hz,1H,3b-H),3.86(dd,J=7.8,5.2Hz,1H,2b-H),3.50(ddd,J=15.6,10.8, 5.5Hz,2H),3.38(t,J=10.9Hz,1H),2.46–2.38(m,1H),2.32–2.23(m,1H),2.13(s,3H,COCH3),2.05(d,J =5.8Hz,6H,COCH3),2.03–1.93(m,1H),1.92–1.70(m,4H),1.69–1.60(m,6H),1.55–1.36(m,3H),1.35–1 .22(m,4H),1.15(d,J=6.2Hz,3H,6a-CH3),1.00–0.95(m,6H),0.94–0.83(m,2H),0.79(d,J=6.4Hz,6H). 13C NMR (150MHz, CDCl3) δ169.2,169.1,169.0,165.00,164.98,164.9,164.5,164.1,163.6,139.3,132.3,132.02,132.00,131.97,131.9,13 1.8,129.1,128.9,128.8,128.74,128.69,128.65,128.63,128.56,128.1,127.93,127.87,127.4,127.3,127.13,127.08,120.8,108.3, 99.0,98.3,96.2,79.8,78.8,76.5,73.0,71.5,70.4,70.1,69.1,68.9,68.7,68.0,65.8,65.5,61.6,61.1,55.5,49.0,40.6,39.2,38.7, 37.4,35.9,35.8,35.6,31.1,30.9,30.8,30.4,29.3,28.7,28.6,27.8,19.9,19.81,19.78,18.2,16.3,16.1,15.3,13.5.HRMS(ESI)Calcd forC 93 H 103 O 26 + [M+H] + :1636.6766, found:1636.6751; C 93 H 102 NaO 26 + [M+Na] + :1658.6586, found:1636.6586; C 93 H 106 NO 26 + [M+NH4] + :1653.7032,found:1653.7023.

[0115] Preparation of compound 2

[0116] Compound 15 was dissolved in a mixed solution of dichloromethane:methanol = 1:2, and 1 M sodium hydroxide was added to adjust the pH to 9-10. The mixture was stirred at room temperature for 4 h. TLC detected that the reaction of the raw material was complete. The solvent was removed by rotary evaporation and separated by silica gel column chromatography (dichloromethane:methanol = 2:1) to obtain compound 2 (24.9 mg, 83%) as a white solid. 1H NMR (400MHz, Pyridine-d5) δ6.27(s,1H),5.32(d,J=5.1Hz,1H),5.20(d,J=7.7Hz,1H),5.05–4.77(m,4H),4.72–4. 52(m,3H),4.47(dd,J=11.7,2.4Hz,1H),4.32(tdd,J=16.6,11.1,5.1Hz,6H),4.20(t,J=9.1Hz,1H),4.08–3.85(m,5 H),3.63–3.55(m,1H),3.51(t,J=10.0Hz,1H),2.84–2.57(m,3H),2.08(ddd,J=25.4,11.7,6.4Hz,2H),2.00–1.77( m,3H),1.76–1.36(m,12H),1.26(q,J=7.7,7.3Hz,2H),1.19–1.00(m,6H),0.99–0.78(m,5H),0.71(d,J=5.1Hz,4H). 13 C NMR(100MHz,Pyridine-d5)δ140.7,121.6,109.1,105.7,101.9,100.2,84. 7,81.0,78.24,78.20,77.4,76.3,75.1,74.8,73.8,72.7,72.4,71.4,70.2 ,69.2,66.7,62.7,62.4,62.3,56.5,50.1,41.8,40.3,39.7,38.6,37.3,37 .0,32.1,31.5,30.4,30.0,29.8,29.1,20.9,19.2,18.4,17.2,16.2,14.9.

[0117] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention are intended to be within the scope of protection of the present invention.

Claims

1. A method for preparing a compound of formula I, characterized in that: The method comprises the steps of performing a glycosidation reaction on compound 4 and compound 3 under the synergistic catalysis of gold trichloride and trimethylacetonitrile to obtain compound 16; reducing the azide group in compound 16 to an amino group before deprotection; and a deprotection step; Among them, the structures of compounds 3, 4, and 16 are shown below: 。 2. A method for preparing a compound represented by formula II, characterized in that: The method comprises the steps of glycosidating compound 4 with compound 5 under the synergistic catalysis of gold trichloride and trimethylacetonitrile to obtain compound 15; and a deprotection step; Among them, the structures of compound 5 and compound 15 are shown below: 。 3. The method according to claim 1, wherein The preparation method of compound 4 comprises the following steps: Compound 6 and compound 7 were glycosylated to obtain compound 13; Converting compound 13 into compound S1; Converting compound S1 into compound 4; Among them, the structures of compounds 6, 7, 13 and S1 are shown below: 。 4. The method according to claim 3, wherein The conversion of compound 13 into compound S1 comprises the following steps: Compound 13 was dissolved in a mixed solution of acetonitrile and water, and ammonium cerium nitrate was added at low temperature to react. After the reaction was completed, compound S1 was obtained.

5. The method according to claim 4, wherein The low temperature is -2~2℃.

6. The method according to claim 3, wherein The conversion of compound S1 into compound 4 comprises the following steps: Compound S1 was dissolved in an organic solvent, and trichloroacetonitrile and 1,8-diazabicyclo[5.4.0]undec-7-ene were added in sequence under an ice-water bath. The temperature was naturally raised to react. After the reaction was completed, compound 4 was obtained.

7. The method according to claim 6, wherein The organic solvent includes dichloromethane.

8. The method according to claim 3, wherein The preparation method of compound 7 comprises the following steps: Converting compound 10 into compound 9; Compound 9 and compound 8 were subjected to glycosylation reaction to obtain compound 11; Converting compound 11 into compound 12; An acylating agent was used to selectively protect the 4- and 6-hydroxyl groups in compound 12 to obtain compound 7; Among them, the structures of compounds 8, 9, 10, 11 and 12 are shown below: 。 9. The method according to claim 8, wherein The conversion of compound 10 into compound 9 comprises the following steps: Compound 10 was dissolved in an organic solvent, 2,6-lutidine was added under a protective atmosphere, and the mixture was stirred at low temperature. Then, tert-butyldimethylsilyl trifluoromethanesulfonate was added and the mixture was stirred to react. After the reaction was completed, compound 9 was obtained.

10. The method according to claim 9, wherein The organic solvent includes N,N-dimethylformamide.

11. The method according to claim 9, wherein The low temperature is -55~-45℃.

12. The method according to claim 8, wherein The conversion of compound 11 into compound 12 represented by the formula comprises the following steps: Tetrabutylammonium fluoride solution was added to compound 11, and the mixture was stirred at room temperature to react. After the reaction was completed, compound 12 was obtained.

13. The method according to claim 12, wherein: In the tetrabutylammonium fluoride solution, the solvent is tetrahydrofuran.

14. The method according to claim 8, wherein The acylating agent is benzoyl cyanide; Utilizing the cyanide effect of benzoyl cyanide, compound 12 was reacted in a one-pot reaction at low temperature to obtain compound 7 with selective protection at the 4 and 6 positions.

15. The method according to claim 14, wherein The low temperature is -80~-75℃.

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